Patients with CNS tumors or known CNS metastases will be excluded from this trial; patients with a history of CNS metastases that have been previously treated may enroll if sequential imaging shows not evidence for active disease; patients with extra axial disease (e.g. skull [bone] metastasis that do not invade the dura) may enroll if there is no evidence for CNS edema associated with the lesion
Patients are eligible if central nervous system (CNS) metastases are adequately treated and neurological symptoms have returned to baseline or are controlled for at least  weeks prior to enrollment; in addition, subjects must be either off corticosteroids, or on a stable or decreasing dose of =<  mg daily prednisone (or equivalent); patients with untreated CNS metastases are eligible if they are not symptomatic and the lesions are less than  cm in size
Patients with central nervous system (CNS) metastases must have all lesions adequately treated with stereotactic radiation therapy, craniotomy, gamma knife therapy, or whole brain radiotherapy, with no subsequent evidence of CNS progression; patients must not have required steroids for at least  days prior to registration
Patients with known or suspected central nervous system (CNS) metastases, untreated CNS metastases, or with the CNS as the only site of disease are excluded; however, subjects with controlled brain metastases will be allowed to enroll; controlled brain metastases are defined as no radiographic progression for at least  weeks following radiation and/or surgical treatment (or  weeks of observation if no intervention is clinically indicated), and off of steroids for at least  weeks, and no new or progressive neurological signs and symptoms
Patients with central nervous system (CNS) metastases with the following exceptions: Patient untreated CNS metastases with  or fewer sites of disease, with no single site larger than  mm, are eligible if they are asymptomatic and not requiring steroids at any dose; patients with asymptomatic CNS metastases may be treated with radiosurgery before or during therapy on trial without treatment delays; patients with treated, symptomatic CNS metastases are eligible if they are neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least  weeks prior to registration AND either off corticosteroids, or on a stable or decreasing dose of =<  mg daily prednisone (or equivalent)
Participants with primary CNS malignancies or tumors with CNS metastases as the only site of disease, will be excluded
Participants with known or suspected CNS metastases, untreated CNS metastases, or with the CNS as the only site of disease (patients with controlled brain metastasis allowed to enroll)
Untreated or symptomatic central nervous system (CNS) metastases (CNS imaging not required). Patients with asymptomatic CNS metastases are eligible provided they have been clinically stable for at least  weeks and do not require intervention such as surgery, radiation, or any corticosteroid therapy for management of symptoms related to CNS disease
Known CNS disease including, but not limited to, metastases
Clinically asymptomatic and stable central nervous system (CNS) metastases are allowed (including untreated CNS metastases) if they have not required increasing doses of steroids or stable doses equivalent to prednisone >  mg daily within  weeks prior to study entry for CNS symptoms
Participants with untreated CNS metastases are excluded. Participants are eligible if CNS metastases are adequately treated and participants are neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least  weeks prior to first treatment
Subjects with symptomatic CNS metastases who are neurologically unstable and/or require an increased dose of steroid to manage CNS symptoms within  week prior to the first day of treatment are excluded\r\n* Subjects with brain or leptomeningeal metastases that do not meet the above criteria are allowed\r\n* Symptomatic disease is allowed as long as symptoms are controlled and stable
Known CNS metastases
Active, non-stable brain metastases or CNS disease
Presence of symptomatic central nervous system (CNS) metastases, or CNS metastases that require local CNS-directed therapy, or increasing doses of corticosteroids within the prior  weeks.
Patients having active central nervous system (CNS) metastases; patients adequately treated and neurologically returned to baseline (except for residual signs of symptoms related to the CNS treated) for at least  weeks prior to enrolment are allowed; in addition, patients must be either off corticosteroids or on a stable or decreasing dose of <  mg daily prednisone or equivalent
Known CNS disease including, but not limited to, metastases
Patients with central nervous system (CNS) metastases must be stable after therapy for CNS metastases (such as surgery, radiotherapy or stereotactic radiosurgery) for at least  weeks and must be off steroid treatment for  weeks prior to study enrollment
Patients with primary CNS tumors or symptomatic CNS metastases who have not undergone surgery and/or radiotherapy and/or who are not neurologically stable;
Previously untreated CNS metastases or progressive CNS metastases
Participants with known or suspected uncontrolled CNS metastases or with the CNS as the only site of active disease
Have metastasis to the CNS that is symptomatic and/or requires therapy with corticosteroids or anti-convulsant medication. However, subjects who have completed treatment (radiation therapy) for CNS metastases and do not require continued treatment with corticosteroids or anti-convulsants may be enrolled in this study.
Participants with known untreated brain metastases should be excluded from this clinical trial; subjects are eligible if CNS metastases are adequately treated and subjects are neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least  weeks prior to study entry; subjects must be either off corticosteroids, or on a stable or decreasing dose of ?  mg daily prednisone (or equivalent) for at least  weeks prior to first study treatment
Subjects with active (i.e. symptomatic or growing) central nervous system (CNS) metastases. Subjects with CNS metastases are eligible if the metastases have been treated with surgery and/or radiotherapy, the subject is off corticosteroids for at least  weeks and the subject is neurologically stable.
No uncontrolled central nervous system (CNS) disease, including parenchymal brain metastases, leptomeningeal disease, or spinal cord compression; patients with asymptomatic untreated brain metastases are eligible; patients with treated CNS disease will be allowed to enroll provided they have clinically confirmed stable disease with >=  weeks since definitive CNS therapy (radiation or surgery) and >=  weeks without systemic steroids; patients may undergo either whole brain radiation or stereotactic radiosurgery prior to study entry
Participants with Central Nervous System (CNS) metastases are not eligible, unless they have completed local therapy for at least  weeks and have discontinued the use of corticosteroids for this indication or are on a tapering regimen of corticosteroids (defined as ? milligrams [mg] prednisolone equivalent) before starting treatment in this study. Any signs (eg, radiologic) or symptoms of brain metastases must be stable for at least  weeks before starting study treatment.
No uncontrolled central nervous system (CNS) disease, including parenchymal brain metastases, leptomeningeal disease, or spinal cord compression; patients with asymptomatic untreated brain metastases are eligible; patients with treated CNS disease will be allowed to enroll provided they have clinically confirmed stable disease with >=  weeks since definitive CNS therapy (radiation or surgery) and >=  weeks without systemic steroids; patients may undergo either whole brain radiation or stereotactic radiosurgery prior to study entry
Participants with primary CNS malignancies, or tumors with CNS metastases as the only site of disease, will be excluded
Patients with treated central nervous system (CNS) metastases will be eligible if not symptomatic, the CNS disease has been stable for a minimum of  weeks and the patient requires less than or equal to the equivalent of  mg/day of dexamethasone
Presence of symptomatic central nervous system (CNS) metastases or CNS metastases that require local CNS-directed therapy (e.g. radiotherapy or surgery) or increasing doses of corticosteroids within the prior  weeks. Patients with treated brain metastases should be neurologically stable (for  weeks post-treatment and prior to study enrollment) and off of steroids for at least  weeks before administration of any study treatment.
Subjects with active central nervous system (CNS) metastases are excluded; if CNS metastases are treated and subjects are at neurologic baseline for at least  weeks prior to enrollment, they will be eligible but will need a brain magnetic resonance imaging (MRI) prior to enrollment; subjects must be off corticosteroids or on a stable or decreasing dose of =<  mg daily prednisone (or equivalent)
Patients with symptomatic central nervous system (CNS) metastases who are neurologically unstable or have required increasing doses of steroids within the  weeks prior to study entry to manage CNS symptoms
If patient has a history of treated asymptomatic CNS metastases they are eligible, provided they meet all of the following criteria: Patient has measurable disease outside CNS; Patient does not have metastases to midbrain, pons, medulla or spinal cord; Patient is not on corticosteroids as therapy for CNS disease (anticonvulsants at a stable dose are allowed); Patient has not had whole-brain radiation within  weeks prior to study enrollment; Patient has stable CNS disease as demonstrated by at least  weeks of stability between the last intervention scan and the study screening scan
Subjects with a history of or active CNS tumors or metastases from non-CNS tumors.
The patient has known active or suspected brain or leptomeningeal metastases. (Central nervous system [CNS] imaging is not required prior to study entry unless there is a clinical suspicion of CNS involvement). Patients with stable, treated brain metastases are eligible provided there is no evidence of CNS disease growth on imaging for at least  months following radiation therapy or other locoregional ablative therapy to the CNS.
Radiographic evidence of CNS metastases
Patients with known brain metastases should be excluded from this clinical trial; patients with brain metastases diagnosed greater than  year prior to study entry may be considered if they received sterilizing therapy to the central nervous system (CNS) (resection or radiation) and have been CNS recurrence-free for the -year period
Symptomatic central nervous system (CNS) metastases that are neurologically unstable or requiring >  mg/day of dexamethasone (or equivalent) to control CNS disease; note: patients with controlled CNS metastases are allowed; radiotherapy or surgery for CNS metastases must have been completed >  weeks prior to study entry; patients must be neurologically stable, having no new neurologic deficits on clinical examination, and no new findings on CNS imaging; steroid use for management of CNS metastases must be at a stable dose for two weeks preceding study entry
Symptomatic central nervous system (CNS) metastases who are neurologically unstable or require increasing doses of steroids or local CNS-directed therapy (such as radiotherapy, surgery or intrathecal chemotherapy) to control their CNS disease
If they have untreated central nervous system (CNS) metastases; patients whose CNS metastases have been treated by surgery or radiotherapy, who are no longer on corticosteroids, and who are neurologically stable may be enrolled in the dose escalation portion of the trial
Subjects with active central nervous system (CNS) metastases causing clinical symptoms or metastases that require therapeutic intervention, including leptomeningeal disease, are excluded. Subjects with a history of treated CNS metastases (by surgery or radiation therapy) are not eligible unless they have fully recovered from treatment, demonstrated no progression for at least  months, and do not require continued steroid therapy.
Subjects with active central nervous system (CNS) metastases with significant neurological compromise or symptoms are excluded. Subjects with a history of treated CNS metastases (by surgery or radiation therapy), who show no evolving new neurological symptoms are eligible for the study.
Known, untreated central nervous system (CNS) or leptomeningeal metastases, or spinal cord compression, patients with any of the above not controlled by prior surgery or radiotherapy, or patients with symptoms suggesting CNS involvement for which treatment is required.
Subjects with active central nervous system (CNS) metastases causing clinical symptoms or metastases that require therapeutic intervention are excluded; subjects with a history of treated CNS metastases (by surgery or radiation therapy) are not eligible unless they have fully recovered from treatment, demonstrated no progression for at least  months, and do not require continued steroid therapy; subjects with CNS metastases incidentally detected during screening which do not cause clinical symptoms and for which standard of care suggests no therapeutic intervention is needed are eligible
Subjects with active central nervous system (CNS) metastases are excluded. Subjects with a history of treated CNS metastases (by surgery or radiation therapy) are not eligible unless they have fully recovered from treatment, demonstrated no progression for at least  months, and do not require continued steroid therapy.
Subjects with symptomatic untreated CNS metastases are excluded\r\n* Subjects are eligible if CNS metastases are asymptomatic or adequately treated and subjects are neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least  weeks prior to first treatment\r\n* In addition, subjects must be either off corticosteroids, or on a stable or decreasing dose of ?  mg daily prednisone (or equivalent) for at least  weeks prior to first treatment
No progression of CNS metastases on MRI or CT for at least  days after last day of prior therapy for the CNS metastases
Patients with treated or untreated asymptomatic CNS metastases may be allowed to enroll.
Central nervous system (CNS) metastases, unless previously treated by either radiation therapy and/or surgical resection, clinically stable for at least  days and off corticosteroids; patients with a history of CNS metastases that are both treated and stably controlled are eligible if all of the following apply: therapy has been administered\r\n(surgery and/or radiation therapy); there is no additional treatment planned for brain metastases; the patient is clinically stable; the patient is off corticosteroids
Participants must not have suspected, known, or progressive CNS metastases, have untreated CNS metastases, or have the CNS as the only site of disease
Subjects with active central nervous system (CNS) metastases are excluded; if CNS metastases are treated and\r\nsubjects are at neurologic baseline for at least  weeks prior to enrollment, they will be eligible but will need a brain magnetic resonance imaging (MRI) prior to enrollment; subjects must be off corticosteroids or on a dose of less than  mg per day
Dose Escalation Cohorts: Active CNS disease, including history of CNS metastases.
MTD/MFD Expansion Cohorts: CNS disease, including history of CNS metastases, that was not stable during the last  months.
Any history of CNS metastases that is not adequately treated (surgery or radiation) >  days prior to registration
Known, untreated central nervous system (CNS) or leptomeningeal metastases, or spinal cord compression, patients with any of the above not controlled by prior surgery or radiotherapy, or patients with symptoms suggesting CNS involvement for which treatment is required.
History of primary CNS malignancy, or leptomeningeal disease or CNS metastases
Subjects with active central nervous system (CNS) metastases are excluded. Subjects are eligible if CNS metastases are adequately treated and subjects are neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least  weeks prior to enrollment. In addition, subjects must be either off corticosteroids, or on a stable or decreasing dose of =<  mg daily prednisone (or equivalent) for  weeks.
Participants with active central nervous system (CNS) metastases, untreated CNS metastases, or with the CNS as the only site of disease are excluded (controlled brain metastases will be allowed to enroll)
Known or suspected central nervous system (CNS) metastases, unless at least one month has passed since last local CNS therapy and there is no evidence for recurrent or progressive CNS disease on follow up imaging; participants may remain on steroids for CNS disease if they are taking a stable dose
Any approved anticancer therapy for treatment purpose is not allowed, or need to be stopped at least  weeks prior to initiation of study treatment; however, the following are allowed: a. endocrine therapy (selective estrogen receptor modulator [SERM], aromatase inhibitor, fulvestrant) b. palliative radiotherapy for bone metastases >  week prior to study treatment c. stable brain metastasis and asymptomatic treated central nervous system (CNS) metastases are allowed, patient must show stable disease by CNS radiographic study >=  weeks from completion of radiotherapy and >=  weeks from discontinuation of corticosteroids
Patients with history of central nervous system (CNS) metastases are eligible if CNS disease has been stable for at least  weeks prior to study registration in the opinion of the investigator and does not require corticosteroids (of any dose) for symptomatic management\r\n* NOTE: Only patients with a known history or indication of CNS disease are required to have CNS imaging prior to study entry
Subjects with CNS metastases are only eligible if the CNS metastases are treated with radiotherapy and/or surgery and subjects are neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment); in addition, subjects must be either off corticosteroids, or on a stable or decreasing dose of =<  mg daily prednisone (or equivalent)
Active CNS metastases; however, patients with CNS metastases will be eligible if they have been treated and are stable without symptoms for  weeks after completion of treatment, with image documentation required, and must be off steroids.
Patients with symptomatic brain metastases are excluded; patients with asymptomatic and treated central nervous system (CNS) metastases may participate in this trial; the patient must have completed any prior treatment for CNS metastases >  days prior to study entry including radiotherapy or surgery; steroids for the treatment of brain metastasis are not permitted, and patients must be stable off steroid treatment for  weeks prior to enrollment
Subjects with active central nervous system (CNS) metastases causing clinical symptoms or metastases that require therapeutic intervention are excluded; subjects with a history of treated CNS metastases (by surgery or radiation therapy) are not eligible unless they have fully recovered from treatment, demonstrated no progression for at least  months, and do not require continued steroid therapy; subjects with CNS metastases incidentally detected during screening which do not cause clinical symptoms and for which standard of care suggests no therapeutic intervention is needed are eligible
Patients with known history of central nervous system (CNS) metastases are eligible if CNS disease has been radiographically and neurologically stable for at least  weeks prior to study registration and do not require corticosteroids (of any dose) for symptomatic management\r\n* NOTE: CNS imaging is only required at baseline for patients with known history of CNS metastases
Active central nervous system (CNS) disease; history of CNS metastases or cord compression is allowable if the patient has been clinically stable for at least  weeks since completion of definitive treatment and is off systemic steroids; in the case of brain metastases, the patient must have stable or improved imaging at least  weeks after completion of definitive treatment; if there is evidence of active leptomeningeal disease, the patient is ineligible
Patients are excluded if they have active CNS metastases. Patients with history of CNS metastases must have MRI scans that show stability of brain metastases for  weeks.
Patients with history of central nervous system (CNS) metastases are eligible if CNS disease has been stable for at least  weeks prior to study registration in the opinion of the investigator and do not require corticosteroids (of any dose) for symptomatic management; NOTE: Patients are not required to have CNS imaging prior to study entry
Subjects with untreated symptomatic central nervous system (CNS) metastases are excluded\r\n* Subjects are eligible if symptomatic CNS metastases are treated and subjects have neurologically returned to baseline (except for residual signs and symptoms related to CNS treatment) for at least  days prior to first dose of study treatment\r\n** Subjects must be off corticosteroids for at least  days prior to first dose of study treatment
Patients with untreated central nervous system (CNS) metastatic disease (including spinal cord and leptomeningeal disease) are excluded\r\n* Note: Subjects with previously treated CNS metastases that are radiographically and neurologically stable for at least  weeks and do not require corticosteroids (of any dose) for symptomatic management are permitted to enroll
mCRPC EXPANSION COHORT: Patients with evidence of CNS metastasis or leptomeningeal disease within  year prior to enrollment will be excluded from this clinical trial; patients with a remote history of brain metastases may be considered if they received sterilizing therapy to the CNS (resection or radiation) and have been CNS progression-free for the -year period; baseline imaging to rule out brain metastases is not required for screening, but should be performed prior to study enrollment if clinically indicated
At screening, patients with =<  CNS metastases and each =<  cm size that were treated with either surgical resection and/or radiation therapy may be included; patients may be included if the largest lesion is =<  cm, and there is no evidence of progressive CNS disease on brain imaging at least  days after definitive treatment, and if the patients with CNS metastases are not taking prednisone >  mg or equivalent daily
At screening, patients with >  cm or >  in number treated CNS metastases may be included if there is no evidence of progressive CNS disease on brain imaging at least  days after treatment with surgery and/or radiation therapy, and if the patients with CNS metastases are not taking prednisone >  mg or equivalent daily
Patients with >  untreated CNS metastases or evidence of peri-tumoral edema will be excluded, or patients with CNS metastases of any status who are taking prednisone >  mg or equivalent steroid daily will be excluded
Patients with =<  untreated CNS metastases but with at least one lesion >  cm or peri-tumoral edema will be excluded, or patients with CNS metastases of any status who are taking prednisone >  mg or equivalent steroid daily will be excluded
Patients with treated CNS metastases >  cm or >  in number will be excluded if there is evidence of progressive CNS disease on brain imaging at least  days after treatment with surgery and/or radiation therapy, or patients with CNS metastases of any status who are taking prednisone >  mg or equivalent will be excluded
For patients with central nervous system (CNS) metastases, metastases must be asymptomatic at the time of day  of the study and meet the following criteria:\r\n* At least  days without progression of CNS metastases as evidenced by magnetic resonance imaging (MRI) or computed tomography (CT) after last day of treatment with radiation to the CNS metastases\r\n* At least  days since last dose of corticosteroids\r\n* Must not have leptomeningeal disease or cord compression
Patients with symptomatic brain metastases are excluded; patients with asymptomatic and treated central nervous system (CNS) metastases may participate in this trial; the patient must have completed any prior treatment for CNS metastases >  days prior to study entry, including radiotherapy or surgery; steroids for the treatment of brain metastasis are not permitted
Known active (untreated) central nervous system (CNS) metastases that require steroids; subjects with CNS metastases who have completed a course of therapy would be eligible for the study provided they are clinically stable for at least  weeks before study entry, defined as:\r\n* No evidence of new or enlarging CNS metastasis or new neurological symptoms attributable to CNS metastases\r\n* Asymptomatic and receiving either no or stable doses of anticonvulsants and total doses of corticosteroids equivalent to  mg of prednisone or less
Known active uncontrolled or symptomatic central nervous system (CNS) metastases, carcinomatous meningitis, or leptomeningeal disease as indicated by clinical symptoms, cerebral edema, and/or progressive growth; patients with a history of CNS metastases or cord compression are eligible if they have been definitively treated (eg, radiotherapy, stereotactic surgery) and are clinically stable off anticonvulsants and steroids for at least  weeks before randomization
Known CNS metastases, unless stable and asymptomatic. Subjects with CNS metastases may be eligible for the study, provided:
Subject has uncontrolled metastases to the central nervous system (CNS) based on head CT or MRI. Subjects with brain metastases may be eligible  weeks after definitive therapy to all known sites of CNS disease provided they are asymptomatic and either off or on a non-increasing dose (in last  weeks) of systemic steroids and not on anticonvulsants for seizure activity directly related to progressive CNS metastases.
Uncontrolled CNS metastases
Patients must not have untreated central nervous system (CNS) metastases; patients whose CNS metastases have been treated by surgery or radiotherapy, who are no longer on corticosteroids, and who are neurologically stable may be enrolled
PHASE I STUDY ELIGIBILITY CRITERIA:\r\nPatients with evidence of central nervous system (CNS) metastasis, spinal cord compression, or leptomeningeal disease within one year prior to enrollment will be excluded from this clinical trial; patients with a remote history of brain metastases may be considered if they received sterilizing therapy to the CNS (resection or radiation) and have been CNS progression-free for the -year period; baseline imaging to rule out brain metastases is not required for screening, but should be performed prior to study enrollment if clinically indicated
Untreated CNS disease, metastases or carcinomatous meningitis. Patients with CNS metastases must be at least  weeks status post prior therapy to the brain and be off all steroids without progressing CNS disease or symptoms.
ALK-positive NSCLC patients with asymptomatic central nervous system (CNS) metastases who are neurologically stable or have not required increasing doses of steroids within the  week prior to study entry to manage CNS symptoms
Patients with symptomatic brain metastases are excluded; however, patients with asymptomatic central nervous system (CNS) metastases may participate in this trial; the patient must have completed any prior local treatment for CNS metastases >  days prior to study entry including radiotherapy or surgery; patients receiving steroids for CNS metastases may not participate on this study
Patients with primary CNS tumors as well as patients with CNS metastases are excluded.
Patient has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. However, patients with CNS metastases who have completed a course of therapy would be eligible for the study provided they are clinically stable for at least  weeks prior to entry as defined as: () no evidence of new or enlarging CNS metastasis on brain imaging within  weeks of enrollment () off steroids for  weeks. Patients with clinically insignificant brain metastases that do not require treatment are eligible
Patients with known active CNS metastases and/or carcinomatous meningitis; however, patients with CNS metastases who have completed a course of therapy would be eligible for the study provided they are clinically stable for at least  month prior to entry as defined as:\r\n* No evidence of new or enlarging CNS metastasis\r\n* Off steroids that are used to minimize surrounding brain edema; patients with clinically insignificant brain metastases that do not require treatment are eligible
Have either previously untreated intracranial CNS metastases or previously treated intracranial CNS metastases with radiologically documented new or progressing CNS lesions.
Known, untreated central nervous system (CNS) or leptomeningeal metastases, or spinal cord compression, patients with any of the above not controlled by prior surgery or radiotherapy, or patients with symptoms suggesting CNS involvement for which treatment is required.
Symptomatic central nervous system (CNS) metastases or asymptomatic CNS metastases that have required steroids within  weeks prior to first dose of study treatment.
Uncontrolled CNS metastases, primary CNS tumors, or solid tumors with CNS metastases as only measurable disease;
Active CNS metastases.
Patients with active, untreated central nervous system (CNS) metastases will be excluded from this clinical trial; patients who have brain metastases that been treated with radiation therapy or surgery will be required to have a washout period of at least  weeks prior to study entry, must be neurologically asymptomatic, and must not require systemic steroids
Patients with CNS metastases with the following exceptions:
Patient untreated CNS metastases with  or fewer sites of disease, with no single site larger than mm, are eligible if they are asymptomatic and not requiring steroids at any dose. Patients with asymptomatic CNS metastases may be treated with radiosurgery before or during therapy on trial without treatment delays.
Patients with treated, symptomatic CNS metastases are eligible if they are neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least  weeks prior to registration AND either off corticosteroids, or on a stable or decreasing dose of ?  mg daily prednisone (or equivalent).
Patients with known CNS metastases (Patients with any clinical signs of CNS metastases must have a CT or MRI of the brain to rule out CNS metastases in order to be eligible for participation in the study). Patients who have had brain metastases treated with radiotherapy or surgically removed with no residual disease confirmed by imaging; patients should be clinically stable and off corticosteroid treatment at least  weeks prior to randomization).
Known symptomatic central nervous system (CNS) metastases requiring steroids. Patients with previously diagnosed CNS metastases are eligible if they () have completed their treatment and have recovered from the acute effects of radiation therapy and/or surgery prior to enrollment, () have discontinued corticosteroid treatment for these metastases for at least  days, and () are neurologically stable;
Known, untreated central nervous system (CNS) or leptomeningeal metastases, or spinal cord compression; patients with any of these not controlled by prior surgery or radiotherapy, or patients with symptoms suggesting CNS involvement for which treatment is required
Patients with seizures due to CNS metastases must be controlled with stable anti-epileptic treatment for >  days
Patients with Gilbert's disease or known CNS metastatic disease. However, patients with CNS metastases who are asymptomatic and have completed a course of therapy are eligible for the study provided that they are clinically stable for  month prior to entry as defined as: () no evidence of new enlarging CNS metastasis, () off steroids or on a stable dose of steroids.
In patients with central nervous system (CNS) metastases, metastases must be asymptomatic at the time of day  of the study and meet the following criteria: \r\n* Brain metastases should have been treated with either whole brain radiation therapy (WBRT), stereotactic radiosurgery (SRS)/gamma-knife, or surgical resection; \r\n* At least  days without progression of CNS metastases as evidenced by magnetic resonance imaging (MRI) or CT from last day of treatment with radiation to the CNS metastases; \r\n* At least  months from surgical resection (if had surgery) with stability on MRI brain at enrollment; \r\n* At least  days since last dose of corticosteroids; \r\n* Must not have leptomeningeal disease or cord compression
Untreated brain metastases or neurologically unstable central nervous system (CNS) metastases (CNS metastases will be considered stable if there are no new nor enlarging lesions for one month, and the patient remains off steroids and anti-epileptics for the same time period)
Any active CNS metastases
Patients with central nervous system (CNS) metastases must be stable after therapy for CNS metastases (such as surgery, radiotherapy or stereotactic radiosurgery) for at least  months and must be off steroid treatment prior to study enrollment
Any active central nervous system (CNS) lesion (i.e., those with radiographically unstable, symptomatic lesions) and/or leptomeningeal metastases; NOTE: patients treated with stereotactic radiotherapy or surgery are eligible if no evidence of CNS disease progression >=  weeks and patients must be off corticosteroid therapy for >=  weeks; NOTE: carcinomatous meningitis is excluded regardless of clinical stability
Patients with a history of prior central nervous system (CNS) metastases or skull lesions with intracranial extension will be required to have a head computed tomography (CT) or magnetic resonance imaging (MRI) at study entry demonstrating no active CNS metastases; patients with skull metastases with associated intracranial soft tissue masses will remain eligible
Known active central nervous system (CNS) metastases or carcinomatous meningitis; patients with CNS metastases including brain metastases who have completed a course of radiotherapy are eligible for the study provided they are clinically stable; however, oral corticosteroids for control of CNS symptoms are not allowed on study
Patient with uncontrolled or symptomatic central nervous system (CNS) metastases; patients with a history of CNS metastases or cord compression are eligible if they have been definitively treated with local therapy and are clinically stable and have discontinued prior treatment with anticonvulsants
At screening, patients with CNS metastases treated with either surgical resection and/or radiation therapy may be included; patients may be included if the largest lesion is =<  cm, and there is no evidence of progressive CNS disease on brain imaging at least  days after treatment
Patients with >  untreated CNS metastases or evidence of peri-tumoral edema will be excluded
Patients with =<  untreated CNS metastases but with at least one lesion >  cm or peri-tumoral edema will be excluded
Patients with treated CNS metastases >  cm or >  in number will be excluded if there is evidence of progressive CNS disease on brain imaging at least  days after treatment with surgery and/or radiation therapy
At screening, patients with =<  treated CNS metastases treated with either surgical resection and/or radiation therapy may be included; patients may be included if the largest lesion is =<  cm, and there is no evidence of progressive CNS disease on brain imaging at least  days after treatment
Patients with >  untreated CNS metastases or evidence of peri-tumoral edema will be excluded
Patients with =<  untreated CNS metastases but with at least one lesion >  cm or peri-tumoral edema will be excluded
Patients with treated CNS metastases >  cm or >  in number will be excluded if there is evidence of progressive CNS disease on brain imaging at least  days after treatment with surgery and/or radiation therapy
PHASE II: Patients with CNS metastases or a history of CNS metastases are ineligible
Patients with active CNS metastases
Patients with active central nervous system (CNS) metastases are excluded; patients with CNS metastases that have been treated must be off steroid treatment for >  months and be asymptomatic; patients that have symptoms to suggest CNS metastases should have a brain magnetic resonance imaging (MRI) within  days of enrollment to confirm the absence of CNS metastases; contrast computed tomography (CT) is acceptable for patients who are unable to undergo a brain MRI
Patients with CNS progression during the trial will be allowed to receive local treatment for CNS metastases and will remain on protocol; trial medications will be held during the time patients are receiving radiation therapy as dictated by their treating physicians
Patients with central nervous system (CNS) tumors or known CNS metastases are not eligible; patients with a history of CNS metastases that have been surgically resected are eligible only if the baseline evaluation shows no evidence of current CNS metastases; patients with any evidence of CNS metastases on baseline evaluation are not eligible, regardless of whether the lesions have been previously treated and/or appear stable
CNS metastases
Known CNS metastases or leptomeningeal disease: For Part , patients with CNS metastases treated with whole brain radiotherapy, gamma knife, and/or surgery who are considered stable by CNS imaging and are not being treated with corticosteroids  weeks prior to study day  may be enrolled. For Part , patients with CNS metastases treated stereotactic radio-surgery (SRS), and/or surgery who are considered stable by CNS imaging for at least  months prior to enrollment and are not being treated with corticosteroids  weeks prior to study day  may be enrolled.
Radiological evidence of CNS metastases
Has active central nervous system (CNS) metastases (including evidence of cerebral edema by MRI, or progression from prior imaging study, or any requirement for steroids, or clinical symptoms of/from CNS metastases) within  days prior to study treatment. Subjects with known CNS metastases must have a baseline MRI scan within  days of study treatment.
Subject has primary central nervous system (CNS) tumor or known CNS metastases and/or history of CNS metastases and/or carcinomatous meningitis; Exception: Subjects are eligible if CNS metastases are adequately treated and subjects are neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least  weeks prior to enrollment. In addition, subjects must be off corticosteroids for  weeks prior to enrollment.
Subjects with radiographic evidence of central nervous system (CNS) metastases as assessed by CT or MRI that are not well controlled (symptomatic or requiring control with continuous corticosteroid therapy [e.g., dexamethasone]) a. Note: Subjects with CNS metastases are permitted to participate in the study if the CNS metastases are medically well-controlled and stable for at least  days after receiving local therapy (irradiation, surgery, etc.)
Subjects with active central nervous system (CNS) metastases are excluded. Subjects with a history of treated CNS metastases (by surgery or radiation therapy) are not eligible unless they have fully recovered from treatment, demonstrated no progression for at least  months, and do not require continued steroid therapy
Have symptomatic CNS metastases (parenchymal or leptomeningeal) at screening or asymptomatic disease requiring an increasing dose of corticosteroids to control symptoms within  days prior to randomization.
Known brain metastases, unless previously treated and patients are neurologically returned to baseline except for residual signs and symptoms related to Central Nervous System (CNS) treatment and CNS lesions are not progressive in size and number for  weeks.
Known active uncontrolled or symptomatic central nervous system (CNS) metastases, carcinomatous meningitis, or leptomeningeal disease as indicated by clinical symptoms, cerebral edema, and/or progressive growth. Patients with a history of CNS metastases or cord compression are eligible if they have been definitively treated with local therapy (eg, radiotherapy, stereotactic surgery) and are clinically stable off anticonvulsants and steroids for at least  weeks before randomization.
Patients with a history of treated brain metastases should be clinically stable for ?  weeks prior to signing the informed consent. Glucocorticoid therapy for central nervous system (CNS) edema is permitted if ?  mg of prednisolone (or equivalent).
Patients with CNS metastases that are symptomatic must have received therapy (surgery, XRT, gamma knife) and be neurologically stable and off of steroids. The patient should be off steroids at least  days before pre-registration. Asymptomatic CNS metastatic disease without associated edema, shift, requirement for steroids or anti-seizure medications are eligible after discussion with the sponsor medical monitor. For patients with a history of CNS metastasis, baseline and subsequent radiological imaging must include evaluation of the brain (MRI preferred or CT with contrast)
Symptomatic central nervous system (CNS) metastases that are neurologically unstable or requiring increasing doses of steroids to control CNS disease\r\n* Note: patients with controlled CNS metastases are allowed; radiotherapy or surgery for CNS metastases must have been completed >  weeks prior to study entry; patients must be neurologically stable, having no new neurologic deficits on clinical examination, and no new findings on CNS imaging; steroid use for management of CNS metastases must be at a stable dose for two weeks preceding study entry
Patient with CNS metastases.
Participants with a history of central nervous system (CNS) metastases prior to the initiation of first-line platinum-based chemotherapy must have received definitive local treatment and have documentation of stable or improved CNS disease status
Known active or suspected brain or leptomeningeal metastases. CNS imaging is not required prior to study entry unless there is a clinical suspicion of CNS involvement. Patients with stable, treated brain metastases are eligible provided there is no evidence of CNS disease growth on imaging for at least  weeks following radiation therapy or other locoregional ablative therapy to the CNS.
Have untreated central nervous system (CNS) metastases. Patients are eligible for study participation if CNS metastases are adequately treated and patients are neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least  days prior to consent. In addition, patients must either be off corticosteroids, or on a stable or decreasing dose of  mg daily prednisone (or equivalent) for at least  days prior to consent.
Presence of symptomatic central nervous system (CNS) metastases, or CNS metastases that require local CNS-directed therapy within prior  weeks.
Asymptomatic and adequately treated CNS metastases are not exclusionary
Patients with history of central nervous system (CNS) metastases are eligible if CNS disease has been radiographically and neurologically stable for at least  weeks prior to study registrations and do not require corticosteroids (of any dose) for symptomatic management
Uncontrolled central nervous system (CNS) metastases; patients are considered to have controlled CNS metastases (and thus eligible) if they have completed local therapy (radiotherapy [XRT] and/or surgery) and are off steroids with clinical and radiographic stability  month from the end of CNS-directed therapy
Participant with uncontrolled or symptomatic central nervous system (CNS) metastases and/or carcinomatous meningitis Participants with controlled and asymptomatic CNS metastases may participate in this trial. The patient must have completed any prior treatment for CNS metastases (must include radiotherapy and/or surgery) ?  days (?  days for stereotactic radiosurgery) and, if on corticosteroid therapy, should be receiving a stable dose of no greater than  mg/d dexamethasone (or equivalent anti-inflammatory potency of another corticosteroid) for at least  days before start of study treatment). Patients must not be receiving corticosteroids for brain metastases.
Subjects with active central nervous system (CNS) metastases are excluded; subjects are eligible if CNS metastases are adequately treated and subjects are neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least  weeks prior to enrollment; in addition, subjects must be either off corticosteroids, or on a stable or decreasing dose of =<  mg daily prednisone (or equivalent) for  weeks
Patients with symptomatic central nervous system (CNS) metastases who are neurologically unstable or require increasing doses of steroids or local CNS-directed therapy to control their CNS disease
Uncontrolled central nervous system (CNS) metastases\r\n* NOTE: metastases have been treated by surgery and/or radiotherapy and patients have been neurologically stable and off of steroids >  weeks are eligible
Have symptomatic CNS metastases that are neurologically unstable or require an increasing dose of corticosteroids.
Dose escalation and MTD/RPD expansion cohort: Patients with symptomatic CNS metastases are excluded. Patients with treated CNS metastases or untreated asymptomatic CNS metastases not requiring immediate local therapy may be eligible. Enrollment of patients with metastases must be approved by the study medical monitor.
Optional CNS disease expansion cohort: Patients with asymptomatic untreated CNS metastases not needing immediate local therapy or patients with progressive CNS disease following local therapy may be eligible with medical monitor approval.
PART B: Patients with CNS metastases are eligible for enrollment if they have no overt evidence of neurological deficits, and are not requiring anti-epileptics or steroids to control their neurological symptoms; patients with known CNS metastases must have relevant CNS imaging performed approximately coincident with body imaging during response assessments
Have central nervous system (CNS) metastases (unless the patient has completed successful local therapy for CNS metastases and has been off corticosteroids for at least  weeks before starting study therapy); brain imaging is required in symptomatic patients to rule out brain metastases, but is not required in asymptomatic patients
Patient with symptomatic central nervous system (CNS) metastases who is neurologically unstable or has required increasing doses of steroids within the  weeks prior to screening to manage CNS symptoms.
Active central nervous system (CNS) disease, metastases or carcinomatous meningitis. Patients with CNS metastases must be at least  weeks status post prior therapy to the brain and be off all steroids without progressing CNS disease.
Brain metastases (unless stable disease > mos. by scan without additional CNS-directed therapy)
Subjects with untreated central nervous system (CNS) metastases are excluded. Subjects are eligible if CNS metastases are asymptomatic or treated and subjects are neurologically returned to baseline for at least  weeks prior to enrollment. In addition, subjects must be either off corticosteroids, or on a stable or decreasing dose of ?mg daily prednisone (or equivalent)
Active central nervous system (CNS) disease\r\n* Subjects with a history of CNS metastases or cord compression are allowable if they have been clinically stable for at least  weeks since completion of definitive treatment, are off steroids (if the steroids were part of the CNS disease treatment), and in the case of brain metastases, have stable or improved imaging at least  weeks after completion of their definitive treatment
Active CNS metastases
In cohort , eligible patients will include those who have CNS disease that is amenable for surgery (typically <  brain metastases and with planned resection by neurosurgery); these patients may include those who have received or not received previous treatment(s) for their CNS
Pathologically (histologically or cytologically) proven diagnosis of a non-hematopoietic malignancy other than small cell lung cancer and germ cell malignancy; direct biopsy of central nervous system (CNS) lesions is not necessarily required although could constitute an allowed site of tissue confirmation as medically prudent; patients who have been disease free for more than  years prior to the appearance of CNS metastases should undergo repeat biopsy of either a systemic metastasis or the CNS metastases to confirm the recurrent malignancy
Patients with evidence or history of central nervous system (CNS) metastases or spinal cord compression, unless prior treatment with surgery or radiotherapy AND no progression of CNS disease within  months prior to treatment
Patient has known active CNS metastases and/or carcinomatous meningitis; however, patients with CNS metastases (including brain metastases) who have completed a course of radiotherapy are eligible for the study provided they are clinically stable; oral corticosteroids for control of CNS symptoms are allowed
Brain metastases permitted in Arms A and B if:\r\n* Central nervous system (CNS)-directed treatment has been given\r\n* No CNS-directed therapy for the past  months, including glucocorticoids AND\r\n* CNS disease has been clinically and radiographically stable for at least  weeks
Central nervous system (CNS) inclusion criteria:\r\n* Subjects without CNS metastases are eligible; Note: brain imaging is not required for asymptomatic subjects without known brain metastatic disease prior to enrollment into the study\r\n* Subjects with untreated asymptomatic CNS metastases not needing immediate local therapy in the opinion of investigator are eligible; for subjects with untreated asymptomatic CNS lesions > . cm magnetic resonance imaging (MRI), discussion with and approval from the lead principle investigator (PI) is required prior to enrollment\r\n* Subjects with stable brain metastases previously treated with radiation therapy or surgery are allowed to enroll, provided that they are off corticosteroids or on stable/tapering dose of corticosteroids and stability of CNS metastatic disease for at least  weeks has been demonstrated, with the last MRI taken within  weeks prior to cycle  day  of the study; relevant records of any CNS treatment must be available to allow for classification of target and non-target lesions
Primary brain tumors or CNS metastases;
Subjects with radiographic evidence of central nervous system (CNS) metastases as assessed by computerized tomography (CT) or magnetic resonance imaging (MRI) that are not well controlled (symptomatic or requiring control with continuous corticosteroid therapy [e.g., dexamethasone]). Note: Subjects with CNS metastases are permitted to participate in the study if the CNS metastases are medically well controlled prior to screening (as assessed by the Investigator) after receiving local therapy (irradiation, surgery, etc.)
Patients with known brain metastases diagnosed within  year will be excluded from this clinical trial; exception: patients with brain metastases diagnosed greater than  year prior to study entry may be considered if they received sterilizing therapy to the central nervous system (CNS) (resection or radiation) and have been CNS progression-free for the -year period
Subjects with central nervous system (CNS) metastases, unless they have been treated and are stable without symptoms for  weeks after completion of treatment and must be off steroids for at least  weeks prior to enrollment
Patients with asymptomatic CNS metastases are allowed
Patients with untreated (primary) or symptomatic CNS (primary or metastatic) malignancies; patients with CNS metastases who have undergone surgery or radiotherapy or who have been on a stable dose of corticosteroids for at least  weeks and whose disease is stable prior to the first scheduled day of dosing will be eligible for the trial.
Subject has symptomatic central nervous system (CNS) metastasis. Subjects with asymptomatic, untreated CNS metastases are allowed. Subjects with previously treated and currently asymptomatic CNS metastases are eligible provided they meet the following:
Known active central nervous system (CNS) metastases. Subjects with CNS metastases who have completed a course of therapy would be eligible for the study provided they are clinically stable for at least  month prior to study entry, defined as:
Patient has symptomatic CNS metastases. Patients with asymptomatic CNS metastases may participate in this trial. The patient must have completed any prior local treatment for CNS metastases ?  days prior to the start of study treatment (including radiotherapy and/or surgery) and must have stable low dose of corticosteroid therapy;
Known, uncontrolled CNS metastases
Evidence of spinal cord compression or current evidence of CNS metastases. Screening CT/MRI of the brain is mandatory. Note: Patients who have been treated for CNS metastases by radiation or gamma knife surgery, who been stable for at least  months and have discontinued high dose corticosteroids will be eligible for protocol participation
Patients with symptomatic central nervous system (CNS) metastases who are neurologically unstable or have required increasing doses of steroids within the  week prior to study entry to manage CNS symptoms
A history of CNS involvement except as follows: Subjects with previously treated CNS metastases that are adequately treated with whole brain radiotherapy, that are neurologically stable, and do not require corticosteroids for symptomatic management for at least  days prior to first dose of study drug. There must be no clear evidence of radiographically active disease for at least  days prior to enrollment.
Has untreated or uncontrolled CNS metastases, including patients who require glucocorticoid therapy for CNS metastases
Patients with symptomatic CNS metastases who are neurologically unstable or have required increasing doses of steroids within the  weeks prior to study entry to manage CNS symptoms.
Symptomatic, untreated, or uncontrolled central nervous system (CNS) metastases or seizure disorder; patients with asymptomatic CNS metastases treated with whole brain radiation (WBRT) or gamma knife radiosurgery (GKR) may be enrolled >=  week after completion of WBRT/GKR provided toxicities are =< Common Toxicity Criteria (CTC) grade I at the time of registration and/or controlled with dexamethasone =<  mg once daily for at least  days at the time of study treatment; patients with symptomatic CNS metastases treated with WBRT/GKR may be enrolled >=  weeks after completion of WBRT/GKR provided toxicities are =< CTC grade  at the time of registration and neurologic symptoms controlled with dexamethasone =<  mg once daily for at least  week at the time of study treatment
Patients with known central nervous system (CNS) or leptomeningeal metastases not controlled by prior surgery or radiotherapy, or patients with symptoms suggesting CNS involvement for which treatment is required.
No 'active' CNS metastases. Prior CNS metastases are allowed, provided adequate palliative therapy has been administered and CNS disease control has been established prior to study entry.  A brain MRI scan, ?  days from day , is required
Known, uncontrolled CNS metastases or primary CNS lymphoma
Patient has known active central nervous system (CNS) metastases and/or carcinomatous meningitis; however, patients with CNS metastases who have completed a course of therapy would be eligible for the study provided they are clinically stable for at least  month prior to entry as defined as: \r\n* No evidence of new or enlarging CNS metastasis \r\n* Off steroids that are used to minimize surrounding brain edema
Patients with known CNS (or leptomeningeal) metastases not controlled by prior surgery or radiotherapy, or patients with symptoms suggesting CNS involvement for which treatment is required.
Symptomatic central nervous system (CNS) malignancy or metastasis. Patients with treated CNS metastases are eligible provided their disease is radiographically stable, asymptomatic, and they are not currently receiving corticosteroids and/or anticonvulsants. Screening of asymptomatic patients without a history of CNS metastases is not required
CNS metastases.
For subjects with solid tumors that are not primary central nervous system (CNS) tumors or NF- associated plexiform neurofibromas subjects with symptomatic or untreated leptomeningeal or brain metastases or spinal cord compression are excluded. NOTE: Subjects previously treated for these conditions that have had stable CNS disease (verified with consecutive imaging studies) for > months, are asymptomatic and are not currently taking corticosteroids, or are on stable dose or decreasing of corticosteroids for at least  days prior to enrolment are permitted.
Known CNS metastases or leptomeningeal disease unless appropriately treated and neurologically stable for at least  weeks
Patients with asymptomatic central nervous system (CNS) metastases will be eligible; for patients that have undergone radiation therapy for their CNS metastases, a minimum of  days must elapse prior to study registration, and patients must have recovered from any adverse events related to radiotherapy with the exception of alopecia and grade  neuropathy
Patients with untreated and/or symptomatic CNS malignancies (primary or metastatic); patients with CNS metastases who have undergone surgery or radiotherapy, whose disease is stable, and who have been on a stable dose of corticosteroids for at least  weeks prior to the first scheduled day of dosing will be eligible for the trial
Newly identified CNS malignancies or documented progression of CNS metastases; subjects will be allowed only if the CNS metastases have been adequately treated with radiotherapy or surgery. For subjects receiving steroid therapy please refer to Section . for allowed steroid maintenance therapy.
Patients with symptomatic central nervous system (CNS) metastases who were neurologically unstable or required increasing doses of steroids to control their CNS disease were excluded.
Subjects with primary central nervous system (CNS) tumors or metastases resected or have received radiation therapy ending at least  weeks prior to study day  are eligible providing they meet all of the following criteria: a) residual neurological symptoms grade ? ; ) no dexamethasone treatment; and c) follow-up MRI shows no new lesions appearing
Untreated central nervous system (CNS) metastases, eligible if they are clinically stable with regard to neurologic function, off all steroids after cranial irradiation at least  weeks prior or after surgical resection performed at least  weeks prior to randomization
Patients who have untreated (primary) or uncontrolled Central Nervous System (CNS) (primary or metastatic) malignancies; patients with CNS metastases who have undergone surgery or radiotherapy or who have been on a stable dose of corticosteroids for at least  weeks and whose disease is stable prior to the first scheduled day of dosing will be eligible for the trial.
Any active central nervous system (CNS) lesion (i.e., those with radiographically unstable, symptomatic lesions) and/or leptomeningeal metastases; however, patient treated with stereotactic radiotherapy, whole brain radiation or surgery are eligible if patient remained without evidence of CNS disease progression >=  weeks; patients must be off corticosteroid therapy for >=  weeks
Presence of symptomatic central nervous system (CNS) metastases, or CNS metastases that require local CNS-directed therapy (such as radiotherapy or surgery).
Have symptomatic central nervous system (CNS) malignancy or metastasis. Asymptomatic participants with treated CNS metastases are eligible for this study if they are not currently receiving corticosteroids to treat CNS metastases
Active untreated brain or leptomeningeal metastases; in patients with treated central nervous system (CNS) metastases, eligible if symptoms controlled for at least  weeks; dexamethasone allowed if total daily dose does not exceed  mg
Patient has symptomatic central nervous system (CNS) metastases or lesions for which treatment is required. Patients who received prophylactic CNS treatment are eligible
Patients with known active brain metastases are excluded; patients with a history of central nervous system (CNS) metastases that have been treated must be stable with no symptoms for >  months after completion of that treatment and off steroid treatment, with image documentation required prior to study enrollment
Known central nervous system metastases causing clinical symptoms or metastases that require therapeutic intervention. Subjects with a history of treated central nervous system (CNS) metastases (by surgery or radiation therapy) are not eligible unless they have fully recovered from treatment, demonstrated no progression for at least  months, and do not require continued steroid therapy. Subjects with CNS metastases incidentally detected during Screening that do not cause clinical symptoms and for which standard of care suggests no therapeutic intervention is indicated, should be discussed with the Sponsor Medical Responsible
Untreated brain or CNS metastases or brain/CNS metastases that have progressed. Subjects with previously treated and clinically stable brain/CNS metastases and who are off all corticosteroids for ?  weeks are eligible.
Active (i.e., symptomatic or growing) central nervous system (CNS) metastases. Subjects with CNS metastases are eligible for the trial if: a. the metastases have been treated by surgery and/or radiotherapy, b. the subject is off corticosteroids (> mg/day) and is neurologically stable for at least  weeks prior to Screening. c. brain MRI completed within  months of Screening.
Subjects with a history of CNS metastases must have completed definitive treatment prior to first dose of study treatment, off or on a stable dose of corticosteroids