Absence of brain metastasis, as confirmed by a negative CT with contrast or magnetic resonance imaging (MRI) scan of the brain, no more than  weeks prior to randomization. Applicable only to metastasectomy participants
Brain magnetic resonance imaging (MRI) with gadolinium within  weeks of study enrollment demonstrating the absence of brain metastases; if an MRI is medically contraindicated or if the patient refuses, a head CT with IV contrast is acceptable
 inoperable brain metastasis or -  brain lesions per screening MRI, confirmed by contrast enhanced MRI amenable to SRS according to the following criteria:
Patients must be free of active brain metastases by contrast-enhanced computerized tomography (CT)/magnetic resonance imaging (MRI) scans within  weeks prior to starting the study drugs; if known to have prior brain metastases, must not have evidence of active (enlarging and/or symptomatic lesions) brain disease on two successive MRI evaluations at least  weeks apart (one of which is at least  weeks prior to starting the study drugs)
Patients must have active brain metastases from NSCLC, confirmed by Gadolinium-enhanced MRI without concomitant leptomeningeal carcinomatosis. Dose of steroids must be stable for  days before the baseline brain MRI. Patients in Arm  must also meet the following inclusion criteria:
Patients must have a brain magnetic resonance imaging (MRI) that is free of active metastases; metastases that have been treated with radiation or surgical resection, are stable for at least  weeks and do not require steroids are eligible
Active brain metastases or leptomeningeal disease. Previously treated brain metastases are allowed provided lesions are stable for at least  months as documented by head CT scan or magnetic resonance imaging (MRI) of the brain. Patients must be off steroids, but anti-convulsants are allowed.
Brain MRI completed within  weeks of Screening.
Patients with known brain metastases or leptomeningeal carcinomatosis will be excluded from this clinical trial. Patients with suspected brain metastases at screening should have an magnetic resonance imaging (MRI) (preferred) or computed tomography (CT) each preferably with intravenous (IV) contrast of the brain prior to study entry.
A diagnostic magnetic resonance imaging (MRI) brain or computed tomography (CT) head demonstrating the presence of - solid tumor brain metastases and lesion to be resected no more than  cm in any direction, performed within  days prior to stereotactic radiosurgery. If multiple lesions are present, then the total brain metastases volume can be no more than  cm^ excluding the lesion to be resected
Patients with more than  brain metastases on MRI brain or CT head
Patients with untreated brain metastases, spinal cord compression, or evidence of symptomatic brain metastases or leptomeningeal disease as noted on computed tomography (CT) or magnetic resonance imaging (MRI) scans are excluded from this clinical trial; while screening brain MRI is not required, it should be performed if clinically indicated at the discretion of the treating investigator; should patient found to have brain metastasis, treatment of brain metastasis must precede the participation in this study
Patients with evidence of symptomatic brain metastases. Patients with treated (surgically excised or irradiated) and stable brain metastases are eligible assuming the patient has adequately recovered from treatment, the treatment was at least  days prior to initiation of study drug, and baseline brain computed tomography (CT) with contrast, or magnetic resonance imaging (MRI) within  days of initiation of study drug, is negative for new or worsening brain metastases
Patients with treated brain metastases will be re-screened (MRI brain or CT head with IV contrast); patients with previously treated brain metastases may participate provided they are stable (without evidence of progression by MRI/CT for at least two weeks prior to the first dose of study drug), have no evidence of new or enlarging brain metastases and are off systemic steroids (=<  mg/day prednisone or equivalent) for at least one weeks prior to enrollment
Patients must be free of active brain metastases by contrast-enhanced CT/magnetic resonance imaging (MRI) scans within  weeks prior to starting the study drugs; if known to have prior brain metastases, must not have evidence of active (enlarging and/or symptomatic lesions) brain disease on MRI evaluation within  weeks from stereotactic radiosurgery (SRS) or whole brain radiation therapy (WBRT) treatment
Brain MRI within one month prior to enrollment
Subjects with brain metastases must have completed treatment, either surgery or radiation,  weeks or longer prior to screening. A brain magnetic resonance imaging (MRI) demonstrating there is no current evidence of progressive brain metastases is required in subjects with previous brain metastasis. Patients with breast tissue expanders may have brain computerized tomography (CT) for assessment.
Known brain metastases, unless these metastases have been treated and stabilized for at least  weeks, prior to enrollment in the study; patients with a history of brain metastases must have a head computed tomography (CT) or magnetic resonance imaging (MRI) scan with contrast to document stable disease for at least  weeks prior to enrollment in the study
All subjects must have at least  distinct lesions as documented by a complete physical examination and imaging studies within  weeks prior to randomization; imaging studies must include a CT scan of the involved disease sites and all known sites of resected disease and brain magnetic resonance (MRI) or CT (brain CT allowable if MRI is contraindicated or if there is no known history of resected brain lesions)
Patients with untreated brain metastases, spinal cord compression, or evidence of symptomatic brain metastases or leptomeningeal disease as noted on computed tomography (CT) or magnetic resonance imaging (MRI) scans should be excluded from this clinical trial; screening brain MRI (or CT if MRI contraindicated) will be required for patients with recurrent NSCLC, TNBC, or SCLC; brain MRI (or CT if MRI contraindicated) is required for PDAC if clinically suspected by patients symptoms or neurological exam; should patient found to have brain metastasis, treatment of brain metastasis must precede the participation in this study; for patients with known and treated brain metastases is allowed in this study if they fulfill the following criteria:\r\n* The lesions have improved or remained stable radiographically and clinically for at least  weeks after completion of brain irradiation or stereotactic brain radiosurgery and off steroids for at least  weeks
Patients with clinically active brain metastases (known or suspected) are excluded unless the brain metastases have been previously treated and are considered stable. Stable brain metastases are defined as no change on CT scan or magnetic resonance imaging (MRI) scan for a minimum of  months AND no change in steroid dose for a minimum of  weeks, unless change due to intercurrent infection or other acute event
Patients who have undergone a resection for brain metastases will be eligible for participation if they have any residual metastases present on post operative magnetic resonance imaging (MRI) of the brain
Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy, radiosurgery, or surgery and stable for at least  weeks prior to enrollment as documented by magnetic resonance imaging (MRI) or computed tomography (CT) imaging; treated brain metastases are defined as having no ongoing requirement for steroids and no evidence of progression or hemorrhage after treatment for at least  weeks prior to enrollment as documented by MRI or CT imaging
Patients with untreated brain metastases, spinal cord compression, or evidence of symptomatic brain metastases or leptomeningeal disease as noted on computed tomography (CT) or magnetic resonance imaging (MRI) scans should not be included on this study; screening imaging to rule out brain metastases is not required for screening, but should be performed prior to study enrollment if clinically indicated; patients with treated brain metastases and resolution of any associated symptoms must demonstrate stable post-therapeutic imaging for at least  months following therapy prior to starting study drug
Brain or central nervous system (CNS) metastases \r\n* Exception: Adequately treated brain metastases documented by baseline computed tomography (CT) or magnetic resonance imaging (MRI) scan that have not progressed since previous scans and do not require corticosteroids (except prednisone =<  mg/day or equivalent) for management of CNS symptoms; a repeated CT or MRI following the identification of CNS metastases (obtained at least  weeks after definitive therapy) must document adequately treated brain metastases\r\n* Subjects with leptomeningeal carcinomatosis are not permitted
Subjects with brain metastasis are excluded from this study, and all patients should have brain imaging (either magnetic resonance imaging [MRI] brain or CT brain with contrast) prior to enrollment
The subject must have a baseline brain magnetic resonance imaging (MRI) scan or CT scan of the head (in patients unable to obtain an MRI) within  days prior to first dose of cabozantinib\r\n* Patients receiving glucocorticoids must be on a stable dose of glucocorticoids during the  days prior to the baseline brain imaging
Patients with known brain metastases should be excluded from this clinical trial; exception: patients with brain metastases will be allowed on study if they have clinically controlled neurologic symptoms, defined as surgical excision and/or radiation therapy followed by  days of stable neurologic function and no evidence of central nervous system (CNS) disease progression as determined by computed tomography (CT) or magnetic resonance imaging (MRI) within  days prior to the first dose of study drug
Patients must be able to have MRI brain imaging
Magnetic resonance imaging (MRI) evidence of - brain metastases, with at least one lesion >  mm and =<  mm in maximal diameter and determined to be appropriate for SRS and gross total resection; all other brain metastases are appropriate for SRS
Active central nervous system (CNS) metastases; magnetic resonance imaging (MRI) (or computed tomography [CT]) required within  months of starting treatment for all tumor types known to commonly metastasize to the brain (i.e. all tumors except pancreas, colorectal, ovarian) and for all patients with CNS symptoms that may represent CNS metastases; metastases which have been treated with radiotherapy >  months prior to start of protocol therapy and are asymptomatic (off steroid therapy for at least  month) may be included; patients must have had normal or stable (if treated, no new lesions) brain imaging (CT or MRI) within the two months prior to day  of study drug\r\n* For the NSCLC expanded cohort only: radiation =<  days prior to day  of study drug; subjects must be off steroids for >  days prior to day  of study drug and anticonvulsants must be discontinued
Patient with treated (surgically excised or irradiated) and stable brain metastases are eligible as long as the treatment was at least  weeks prior to initiation of study drug and baseline brain computed tomography (CT) with contrast or magnetic resonance imaging (MRI) within  weeks of initiation of study drug is negative for new brain metastases. Subjects with stable brain metastases must not require therapy with corticosteroids
Patients with untreated brain metastases are excluded. However, patients with metastatic central nervous system (CNS) tumors may participate in this trial, if the patient is >  weeks from therapy completion (including [incl.] radiation and/or surgery), is clinically stable at the time of study entry and is receiving a stable or decreasing dose of corticosteroid therapy; brain magnetic resonance imaging (MRI) or head computed tomography (CT) is required at screening for patients with known brain metastases
Greater than  presumed melanoma brain metastases on contrast-enhanced brain MRI scan obtained no greater than  weeks prior to study registration
lesions assessed by follow-up scan (or MRI if MRI performed before brain therapy) ?  month after brain therapy are considered under control at baseline
Clinically active known brain metastasis unless the brain metastases have been previously treated and are considered stable. Stable brain metastases are defined as no change on computed tomography (CT) scan or magnetic resonance imaging (MRI) for a minimum of  months and no change in steroid dose for a minimum of  weeks prior to starting the trial.
Patients must have measurable disease in the brain, defined as at least one lesion that can be accurately measured in at least one dimension as >=  mm by brain magnetic resonance imaging (MRI); MRI of the brain (with and without gadolinium enhancement) is to be performed using standard -mm slices with .-mm spacing for comparison to subsequent MRI scans
Patients are ineligible if they have any currently active central nervous system (CNS) metastases; patients who have treated brain metastases (with either surgical resection or stereotactic radiosurgery) that have been stable on head magnetic resonance imaging (MRI) or contrast computed tomography (CT) scan for at least  weeks following treatment and within  weeks prior to randomization are eligible; patients must not have taken any steroids =<  days prior to randomization for the purpose of managing their brain metastases; patients with only whole brain irradiation for treatment of CNS metastases will be ineligible
Patients with untreated brain metastases, spinal cord compression, or evidence of symptomatic brain metastases or leptomeningeal disease as noted on computed tomography (CT) or magnetic resonance imaging (MRI) scans should not be included on this study, since neurologic dysfunction may confound the evaluation of neurologic and other adverse events; patients with treated brain metastases and resolution of any associated symptoms must demonstrate stable post-therapeutic imaging for at least  months following therapy prior to starting study drug
Patients must have histologically or cytologically confirmed malignancy (not leukemia or lymphoma); there must be metastatic brain disease apparent on magnetic resonance imaging (MRI) which offers a medical indication for brain radiation
Patients must have a brain magnetic resonance imaging (MRI) or computed tomography (CT) (with and without contrast) that is free of active metastases; metastases that have been treated with radiation or surgical resection, are stable for at least  weeks and do not require steroids are eligible
Pretreatment brain CT with contrast or brain magnetic resonance imaging (MRI) to rule out metastases
Patients must be free of brain metastasis by contrast-enhanced computed tomography (CT)/magnetic resonance imaging (MRI) scans within  weeks prior to enrollment; if known to have prior brain metastases, must not have evidence of active brain disease after definitive therapy (surgery, radiation therapy or stereotactic radiosurgery) on two successive MRI evaluations at least  months apart (one of which is =<  weeks prior to starting the study drugs)
CT scan of the brain (contrast is recommended unless medically contraindicated) or MRI of the brain within  weeks prior to registration
Exception: Adequately treated brain metastases documented by baseline CT or MRI scan that has not progressed since previous scans and that does not require corticosteroids (except prednisone ?  mg/day or equivalent) for management of CNS symptoms. A repeat CT or MRI following the identification of CNS metastases (obtained at least  weeks after definitive therapy) must document adequately treated brain metastases.
All patients must have a CT or magnetic resonance imaging (MRI) of the brain within  days prior to registration; the brain CT or MRI should be performed with intravenous contrast (unless contraindicated)
Patients with brain metastases are ineligible; all patients must have a pretreatment CT or MRI scan of the brain to evaluate for central nervous system (CNS) disease within  days prior to registration
Patients with known active brain metastases should be excluded from this clinical trial; patients with prior treated brain metastases are allowed, providing that they were not accompanied by seizures and that a baseline brain magnetic resonance imaging (MRI) scan prior to study entry demonstrates no current evidence of brain metastases; all patients with central nervous system (CNS) metastases must be stable for >  months after treatment and off steroid treatment prior to study enrollment
Subjects with brain metastases (subjects must have a CT scan or MRI of the head within  days prior to enrollment to rule out brain metastases), uncontrolled seizure disorder, or active neurologic disease
Known brain or leptomeningeal disease (CT or MRI scan of the brain required only in case of clinical suspicion of central nervous system involvement).
Magnetic resonance imaging (MRI) or CT scans of brain if there are symptoms or signs suggesting brain metastases, must be done within  weeks prior to study entry
Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy, radiosurgery, or surgery and stable for at least  weeks prior to enrollment as documented by magnetic resonance imaging (MRI) or computed tomography (CT) imaging; treated brain metastases are defined as having no ongoing requirement for steroids and no evidence of progression or hemorrhage after treatment for at least  weeks prior to enrollment as documented by MRI or CT imaging
Patients with untreated brain metastases, spinal cord compression, or evidence of symptomatic brain metastases or leptomeningeal disease as noted on computed tomography (CT) or magnetic resonance imaging (MRI) scans are ineligible; screening imaging to rule out brain metastases is not required for screening, but should be performed prior to study enrollment if clinically indicated; patients with treated brain metastases must demonstrate stable post-therapeutic imaging and resolution of any associated symptoms and must be stably off steroids with no symptoms for at least  months following therapy prior to starting study drug
The baseline brain MRI/CT must be performed less than  days prior to initiation of study treatment; otherwise it must be repeated
A brain MRI/CT must be performed less than  days prior to initiation of study treatment; otherwise it must be repeated
Brain metastases per magnetic resonance imaging (MRI) or computed tomography (CT)\r\n* Note: patients who have had therapy for brain metastasis (i.e., surgical resection, whole brain radiation, or stereotactic radiosurgery [SRS] even if stable) are not eligible
at least  weeks without new brain metastases as evidenced by MRI/CT
Patient with central nervous system (CNS) metastasis are required to have stable disease documented by being off treatment (surgery, radiation therapy) for at least  weeks, and four () weeks is preferred; a contrast enhanced brain computed tomography (CT) or brain magnetic resonance imaging (MRI) is required within  days of enrollment; patients with brain metastases who qualify for protocol therapy will be included in Cohort  (ineligible for treatment with bevacizumab)
Subjects must be free of known brain metastases by contrast-enhanced computed tomography (CT)/magnetic resonance imaging (MRI) scans or have successfully-treated brain metastases and be asymptomatic for more than  month
Absence of brain metastases as confirmed by imaging of the brain by MRI or CT brain with contrast performed at baseline screening
Four or fewer brain metastases (as defined on the pre-operative MRI or CT brain scan) and status post resection of one of the lesions
Histologically confirmed HER-positive (immunohistochemistry [IHC] + or fluorescence in situ hybridization [FISH] amplified; by clinical assay on either primary or metastatic tumor) adenocarcinoma of the breast with at least one progressive and/or new metastatic brain lesion (>=  mm on radiographic imaging); patients in whom brain metastases (BM) are asymptomatic and detected during routine brain magnetic resonance imaging (MRI) screening per institutional protocols are eligible
Patients with solitary brain metastases previously treated with surgery or stereotactic radiosurgery (+/- whole brain radiation therapy [WBRT]) and currently controlled at the time of study enrollment are also eligible but must have an magnetic resonance imaging (MRI) within  days prior to study registration; patients with a history of multiple brain metastases must have an MRI showing no active brain metastases within  days prior to study registration
History of leptomeningeal carcinomatosis or active brain metastases receiving concurrent treatment inclusive of but not limited to surgery, radiation and/or corticosteroids; Note: brain metastases that have been treated for anticancer purposes where there has been no magnetic resonance imaging (MRI) evidence of progression for at least  weeks after treatment are permitted on study
Subjects with known brain metastases and contraindications to undergo contrast MRI imaging of the brain are excluded from the study
Patients with untreated brain metastases, spinal cord compression, or evidence of symptomatic brain metastases or leptomeningeal disease as noted on computed tomography (CT) or MRI scans should not be included on this study; screening imaging to rule out brain metastases is not required for screening, but should be performed prior to study enrollment if clinically indicated; patients with treated brain metastases and resolution of any associated symptoms must demonstrate stable post-therapeutic imaging for at least  months following therapy prior to starting study drug
Patients with a history or clinical evidence of brain metastasis must have completed radiation therapy or surgical treatment of brain lesions and have no evidence of central nervous system (CNS) progression for at least eight weeks at the time of registration; patients must not require corticosteroids for treatment of cerebral edema from brain metastases; patients must be evaluated with a head magnetic resonance imaging (MRI) within  weeks prior to registration
Patient should undergo brain imaging (CT scan or magnetic resonance imaging [MRI]) to rule out brain metastases
Presence of parenchymal brain metastases; patients with neurological symptoms must have a CT or magnetic resonance imaging (MRI) of the brain showing no metastases within  days of enrollment
If patient has a history of brain metastases or leptomeningeal disease, lesions must be stable for at least  months (as documented by either head computed tomography [CT] or brain magnetic resonance imaging [MRI])
Patients with history of brain metastases can be enrolled at a minimum of  weeks following the completion of surgery, gamma knife or whole brain radiotherapy; repeat brain magnetic resonance imaging (MRI) not required for eligibility
Patients must be free of active brain metastasis by contrast-enhanced computed tomography/magnetic resonance imaging (CT/MRI) scans within  weeks prior to enrollment; if known to have prior brain metastases, these must have been adequately managed with standard of care radiation therapy, stereotactic radiosurgery or surgery prior to registration on the study
Evidence of active brain metastases, including leptomeningeal involvement (prior evidence of brain metastasis are permitted only if treated and stable and off therapy for >=  weeks prior to signing informed consent form; magnetic resonance imaging of the brain (or computed tomography scan w/contrast) is preferred for diagnosis
Evidence of active brain metastases, including leptomeningeal involvement (prior evidence of brain metastasis are permitted only if treated and stable and off therapy for at least days prior to signing ICF). MRI of the brain (or CT scan w/contrast) is preferred for diagnosis.
Patients must be free of active brain metastases by contrast-enhanced computed tomography (CT)/magnetic resonance imaging (MRI) scans within  weeks prior to starting the study drugs; if known to have prior brain metastases, must not have evidence of active (enlarging and/or symptomatic lesions) brain disease on two successive MRI evaluations at least  months apart (one of which is at least  weeks prior to starting the study drugs)
Presence of any brain metastases detected by MRI or CT with i.v. contrast of the brain at screening.
Patients must be free of brain metastasis by contrast-enhanced CT/magnetic resonance imaging (MRI) scans within  weeks prior to enrollment; if known to have prior brain metastases, must not have evidence of active brain disease after definitive therapy (surgery, radiation therapy, or stereotactic radiosurgery) on two successive MRI evaluations at least  months apart (one of which is =<  weeks prior to starting the study drugs)
History or evidence of brain metastases on MRI or head CT if MRI is not able to be performed.
Central nervous system (CNS) metastases: Patients who remain asymptomatic after successful definitive treatment of brain metastases (i.e., surgical resection, curative whole brain irradiation, stereotactic radiation therapy, or a combination of these) demonstrating stable or improved radiographic appearance on magnetic resonance imaging (MRI) scan >=  months after completion of treatment and no signs of cerebral edema are eligible
History and/or current evidence of CNS metastases. Baseline MRI scan by Independent Reviewer to confirm no brain mets;
Patients may have brain metastases if all lesions have been treated with stereotactic radiation therapy, craniotomy, or gamma knife therapy with no evidence of progression (demonstrated by identical imaging modality for  consecutive assessments/scans [magnetic resonance imaging (MRI) or CT scans], at least  weeks apart) and have not required steroids for at least  days prior to registration
No definitive evidence of brain metastases on brain computed tomography (CT) scan or brain magnetic resonance imaging (MRI) <  month prior to study entry
Brain metastases outside a -mm margin around either hippocampus must be visible on contrast-enhanced magnetic resonance imaging (MRI) performed =<  days prior to Step  registration; an allowed exception, regarding ability to image brain metastases, would be that patients who had undergone radiosurgery or surgical resection and are planning adjuvant WBRT do not have to have visible disease but do need a pre-surgery MRI or computed tomography (CT) scan demonstrating brain metastases; however, the brain metastases could not have been within  mm of either hippocampus
Inability to get brain MRI
Patients with - measurable brain metastases on a diagnostic-quality contrast-enhanced MRI obtained within  days prior to registration
Patients must have a magnetic resonance imaging (MRI) or CT brain within  weeks prior to study entry to rule out asymptomatic brain metastases
Radiologic evidence of new and/or progressive brain metastases (>=  mm in longest dimension) by MRI imaging of the brain
Has known active parenchymal central nervous system (CNS) metastases that are symptomatic, and/or more than one lesions, and/or their largest diameter is > -mm and/or require antiepileptic drugs or corticosteroids; patients with carcinomatous meningitis are also excluded; exceptions are: subjects with previously treated brain metastases provided they are stable (without evidence of progression by imaging) for at least  weeks prior to C-AMT and any neurologic symptoms have returned to baseline, have no evidence of new or enlarging brain metastases, and are not using ongoing steroids for at least  days prior to C-AMT; patients with active (i.e. not treated with stereotactic radiosurgery), single, asymptomatic, up to -mm in largest diameter brain metastases (measured either by brain magnetic resonance imaging [MRI] with IV contrast or head CT with IV contrast measured within  weeks prior to C-AMT) are allowed
Three different adult patient groups will be eligible for inclusion in this study: \r\n* Group : Adult patients with compelling evidence of primary brain tumor based on clinical and magnetic resonance imaging (MRI) or computed tomography (CT) imaging characteristics that have not yet received surgery, histological diagnosis, or any tumor-directed therapy; such evidence will include: MRI or CT scan-documented mass lesion within the brain, accompanied by anatomically appropriate neurological signs and symptoms, in the absence of a probable competing diagnosis such as brain abscess or primary intracranial hematoma\r\n* Group : Newly diagnosed primary malignant brain tumors (World Health Organization [WHO] grade II-IV glial-based tumors) who have not had a complete surgical resection and by contrast MRI or CT have residual tumor >= . cm in diameter and will be receiving radiotherapy and/or chemotherapy\r\n* Group : Patients with probable or possible recurrent primary brain tumor as determined by standard clinical criteria or MRI or CT imaging; the abnormality must be >= . cm in diameter by contrast MRI or CT or show changes on non-enhancing MRI sequences (T or fluid-attenuated inversion recovery [FLAIR])
Patient must have newly diagnosed brain metastases visible on brain magnetic resonance imaging (MRI); a biopsy of the lesion is not required as long as the patient has a biopsy-proven malignancy elsewhere and a clinician deems the lesion to be metastatic