Hello,
Sep Policy is work only in Normal Mode as per design. Safe Mode is use for troubleshooting part that why Sep client and policy not work because if it can enable in safe mode then while using the troubleshoot tool it create issue in running.
It only disable through group policy. If you want to disable use the same option.
Check the below thread
https://www-secure.symantec.com/connect/forums/need-block-usb-safe-mode-safe-mode-networking