Is purging %SYSTEMROOT%\assembly\temp safe?
Solution 1:
Before you try purging this folder you have to consider that files in this folder can be used by certain .Net-applications. That being said you should check if there is any .Net application not cleaning up properly (maybe a self programmed one or a third-party-program).
You should also consider a reboot of the server because this should cause processes to end and Windows to clean that directory at least partially.
This folder can grow in size because of software-installation and -updates not cleaning up properly. However, SOME application might use files in this folder and you cannot rely on those applications to properly block the files from being deleted which can lead to malfunctions.
Purging the folder should be the last solution because it's just fighting the symptoms and not the reason that led to the folder growing that big.