['breast cancer', 'brain tumor - metastatic']
['cabozantinib', 'trastuzumab']

        Inclusion Criteria:

          -  Patients must have histologically or cytologically confirmed invasive breast cancer,
             with stage IV disease.

          -  New or progressive CNS lesions, as assessed by the patient's treating physician.

          -  For patients who have received prior cranial radiation, no increase in corticosteroid
             dose in the week prior to the baseline brain MRI

          -  Discontinued prior therapy (with the exception of trastuzumab for patients with HER2+
             breast cancer)

          -  Recovery to baseline or ≤ Grade 1 CTCAE v.4.0 from toxicities related to any prior
             treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive
             therapy;

          -  The subject has an ECOG performance status of 0 or 1

          -  Patients must have normal organ and marrow function and laboratory values as follows
             within 4 days before the first dose of cabozantinib

          -  Sexually active subjects (men and women) must agree to use medically accepted barrier
             methods of contraception (e.g., male or female condom) during the course of the study
             and for 4 months after the last dose of study drug(s)

          -  Subjects of childbearing potential must not be pregnant at screening.

          -  Patients on bisphosphonates may continue receiving bisphosphonate therapy during
             study. Patients wanting to initiate bisphosphonate therapy may do so.

          -  The subject has had an assessment of all known disease sites eg, by computerized
             tomography (CT) scan, magnetic resonance imaging (MRI), bone scan as appropriate,
             within 28 days before the first dose of cabozantinib

        Exclusion Criteria:

          -  The subject has received cabozantinib or another c-Met inhibitor (please note ARQ 197
             is not considered a MET inhibitor for purposes of this study given data to suggest it
             inhibits tubulin)

          -  The subject has uncontrolled, significant intercurrent or recent illness

          -  Leptomeningeal disease as the only site of CNS involvement

          -  Known contraindication to MRI with gadolinium contrast, such as cardiac pacemaker,
             shrapnel, or ocular foreign body

          -  More than 2 seizures over the last 4 weeks prior to study entry

          -  Grade 1 or higher CNS hemorrhage on baseline brain MRI, or history of grade 2 or
             higher CNS hemorrhage within 12 months

          -  The subject has tumor in contact with, invading or encasing any major blood vessels

          -  The subject has evidence of tumor invading the GI tract (esophagus, stomach, small or
             large bowel, rectum or anus), or any evidence of endotracheal or endobronchial tumor
             within 28 days before the first dose of cabozantinib

          -  The subject requires concomitant treatment, in therapeutic doses, with anticoagulants.
             Low dose aspirin (≤ 81 mg/day), low-dose warfarin ( ≤1 mg/day), and prophylactic LMWH
             are permitted.

          -  The subject has prothrombin time (PT)/INR or partial thromboplastin time (PTT) test
             ≥1.3 × the laboratory ULN within 7 days before the first dose of cabozantinib.

          -  Inability to swallow intact tablets

          -  Diagnosis of another malignancy within 2 years before the first dose of cabozantinib,
             except for superficial skin cancers, or localized, low grade tumors deemed cured and
             not treated with systemic therapy

          -  Subjects with clinically relevant ongoing complications from prior radiation therapy
             are not eligible

          -  The subject is known to be positive for the human immunodeficiency virus (HIV)

          -  Subjects with clinically relevant ongoing complications from prior surgery are not
             eligible

          -  QTcF > 500 msec on average of screening EKGs performed within 28 days of first dose of
             cabozantinib. Three EKGs must be performed at screening. If the average of these three
             consecutive results for QTcF is > 500 msec, the subject is ineligible.

          -  Active infection requiring IV antibiotics at Day 1 of cycle 1

          -  No prior lapatinib within 7 days prior to initiation of protocol treatment

          -  Previously identified allergy or hypersensitivity to components of the cabozantinib
             formulations

          -  The subject requires chronic concomitant treatment with strong CYP3A4 inducers
      